Scalable Manufacture of Built-to-Order Nanomedicine: Spray-Assisted Layer-by-Layer Functionalization of PRINT Nanoparticles

Scalable methods, PRINT particle fabrication, and spray-assisted Layer-by-Layer deposition are combined to generate uniform and functional nanotechnologies with precise control over composition, size, shape, and surface functionality. A modular and tunable approach towards design of built-to-order nanoparticle systems, spray coating on PRINT particles is demonstrated to achieve technologies capable of targeted interactions with cancer cells for applications in drug delivery.National Cancer Institute (U.S.) (Center for Cancer Nanotechnology Excellence Grant 5 U54 CA151884-02)National Science Foundation (U.S.). Graduate Research FellowshipNatural Sciences and Engineering Research Council of Canada (Postdoctoral Fellowship

Efficacy and pharmacokinetics of a modified acid-labile docetaxel-PRINT ® nanoparticle formulation against non-small-cell lung cancer brain metastases

Particle Replication in Nonwetting Templates (PRINT®) PLGA nanoparticles of docetaxel and acid-labile C2-dimethyl-Si-Docetaxel were evaluated with small molecule docetaxel as treatments for non-small-cell lung cancer brain metastases

Preparation and biological evaluation of synthetic and polymer-encapsulated congeners of the antitumor agent pactamycin: Insight into functional group effects and biological activity

The synthesis and biological analysis of a number of novel congeners of the aminocyclopentitol pactamycin is described. Specific attention was paid to the preparation of derivatives at crucial synthetic branch points of the parent structure, and biological assays revealed a number of insights into the source of pactamycin’s biological activity. Additionally, the encapsulation of pactamycin and select derivatives into the PRINT© nanoparticle technology was investigated as a proof-of-concept, and evidence of bioactivity modulation through nanoparticle delivery is demonstrated. This work has provided heretofore unrealized access to a large number of novel compounds for further evaluation

Docetaxel-Loaded PLGA Nanoparticles Improve Efficacy in Taxane-Resistant Triple-Negative Breast Cancer

Novel treatment strategies, including nanomedicine, are needed for improving management of triple-negative breast cancer. Patients with triple-negative breast cancer, when considered as a group, have a worse outcome after chemotherapy than patients with breast cancers of other subtypes, a finding that reflects the intrinsically adverse prognosis associated with the disease. The aim of this study was to improve the efficacy of docetaxel by incorporation into a novel nanoparticle platform for the treatment of taxane-resistant triple-negative breast cancer. Rod-shaped nanoparticles encapsulating docetaxel were fabricated using an imprint lithography based technique referred to as Particle Replication in Nonwetting Templates (PRINT). These rod-shaped PLGA-docetaxel nanoparticles were tested in the C3(1)-T-antigen (C3Tag) genetically engineered mouse model (GEMM) of breast cancer that represents the basal-like subtype of triple-negative breast cancer and is resistant to therapeutics from the taxane family. Thi..

Nanoparticle drug loading as a design parameter to improve docetaxel pharmacokinetics and efficacy

Nanoparticle (NP) drug loading is one of the key defining characteristics of a NP formulation. However, the effect of NP drug loading on therapeutic efficacy and pharmacokinetics has not been thoroughly evaluated. Herein, we characterized the efficacy, toxicity and pharmacokinetic properties of NP docetaxel formulations that have differential drug loading but are otherwise identical. Particle Replication in Non-wetting Templates (PRINT®), a soft-lithography fabrication technique, was used to formulate NPs with identical size, shape and surface chemistry, but with variable docetaxel loading. The lower weight loading (9%-NP) of docetaxel was found to have a superior pharmacokinetic profile and enhanced efficacy in a murine cancer model when compared to that of a higher docetaxel loading (20%-NP). The 9%-NP docetaxel increased plasma and tumor docetaxel exposure and reduced liver, spleen and lung exposure when compared to that of 20%-NP docetaxel

Measurement of Branching Fraction and Dalitz Distribution for B0->D(*)+/- K0 pi-/+ Decays

We present measurements of the branching fractions for the three-body decays B0 -> D(*)-/+ K0 pi^+/-$and their resonant submodes$B0 -> D(*)-/+ K*+/- using a sample of approximately 88 million BBbar pairs collected by the BABAR detector at the PEP-II asymmetric energy storage ring. We measure: B(B0->D-/+ K0 pi+/-)=(4.9 +/- 0.7(stat) +/- 0.5 (syst)) 10^{-4} B(B0->D*-/+ K0 pi+/-)=(3.0 +/- 0.7(stat) +/- 0.3 (syst)) 10^{-4} B(B0->D-/+ K*+/-)=(4.6 +/- 0.6(stat) +/- 0.5 (syst)) 10^{-4} B(B0->D*-/+ K*+/-)=(3.2 +/- 0.6(stat) +/- 0.3 (syst)) 10^{-4} From these measurements we determine the fractions of resonant events to be : f(B0-> D-/+ K*+/-) = 0.63 +/- 0.08(stat) +/- 0.04(syst) f(B0-> D*-/+ K*+/-) = 0.72 +/- 0.14(stat) +/- 0.05(syst)Comment: 7 pages, 3 figures submitted to Phys. Rev. Let

Study of e+e- --> pi+ pi- pi0 process using initial state radiation with BABAR

The process e+e- --> pi+ pi- pi0 gamma has been studied at a center-of-mass energy near the Y(4S) resonance using a 89.3 fb-1 data sample collected with the BaBar detector at the PEP-II collider. From the measured 3pi mass spectrum we have obtained the products of branching fractions for the omega and phi mesons, B(omega --> e+e-)B(omega --> 3pi)=(6.70 +/- 0.06 +/- 0.27)10-5 and B(phi --> e+e-)B(phi --> 3pi)=(4.30 +/- 0.08 +/- 0.21)10-5, and evaluated the e+e- --> pi+ pi- pi0 cross section for the e+e- center-of-mass energy range 1.05 to 3.00 GeV. About 900 e+e- --> J/psi gamma --> pi+ pi- pi0 gamma events have been selected and the branching fraction B(J/psi --> pi+ pi- pi0)=(2.18 +/- 0.19)% has been measured.Comment: 21 pages, 37 postscript figues, submitted to Phys. Rev.

Measurement of the quasi-elastic axial vector mass in neutrino-oxygen interactions

The weak nucleon axial-vector form factor for quasi-elastic interactions is determined using neutrino interaction data from the K2K Scintillating Fiber detector in the neutrino beam at KEK. More than 12,000 events are analyzed, of which half are charged-current quasi-elastic interactions nu-mu n to mu- p occurring primarily in oxygen nuclei. We use a relativistic Fermi gas model for oxygen and assume the form factor is approximately a dipole with one parameter, the axial vector mass M_A, and fit to the shape of the distribution of the square of the momentum transfer from the nucleon to the nucleus. Our best fit result for M_A = 1.20 \pm 0.12 GeV. Furthermore, this analysis includes updated vector form factors from recent electron scattering experiments and a discussion of the effects of the nucleon momentum on the shape of the fitted distributions.Comment: 14 pages, 10 figures, 6 table

Measurement of the Branching Fraction for B- --> D0 K*-

We present a measurement of the branching fraction for the decay B- --> D0 K*- using a sample of approximately 86 million BBbar pairs collected by the BaBar detector from e+e- collisions near the Y(4S) resonance. The D0 is detected through its decays to K- pi+, K- pi+ pi0 and K- pi+ pi- pi+, and the K*- through its decay to K0S pi-. We measure the branching fraction to be B.F.(B- --> D0 K*-)= (6.3 +/- 0.7(stat.) +/- 0.5(syst.)) x 10^{-4}.Comment: 7 pages, 1 postscript figure, submitted to Phys. Rev. D (Rapid Communications

Measurement of the B+ --> p pbar K+ Branching Fraction and Study of the Decay Dynamics

With a sample of 232x10^6 Upsilon(4S) --> BBbar events collected with the BaBar detector, we study the decay B+ --> p pbar K+ excluding charmonium decays to ppbar. We measure a branching fraction Br(B+ --> p pbar K+)=(6.7+/-0.5+/-0.4)x10^{-6}. An enhancement at low ppbar mass is observed and the Dalitz plot asymmetry suggests dominance of the penguin amplitude in this B decay. We search for a pentaquark candidate Theta*++ decaying into pK+ in the mass range 1.43 to 2.00 GeV/c2 and set limits on Br(B+ --> Theta*++pbar)xBr(Theta*++ --> pK+) at the 10^{-7} level.Comment: 8 pages, 7 postscript figures, submitted to Phys. Rev. D (Rapid Communications